Tissue biomarkers of breast cancer and their association with conventional pathologic features

Chung, L; Shibli, S; Moore, K; Elder, EE; Boyle, FM; Marsh, DJ; Baxter, RC

Tissue biomarkers of breast cancer and their association with conventional pathologic features

Chung, L Shibli, S Moore, K Elder, EE Boyle, FM Marsh, DJ

Baxter, RC

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Publication Type:: Journal Article
Citation:: British Journal of Cancer, 2013, 108 (2), pp. 351 - 360
Issue Date:: 2013-02-01

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Field	Value	Language
dc.contributor.author	Chung, L	en_US
dc.contributor.author	Shibli, S	en_US
dc.contributor.author	Moore, K	en_US
dc.contributor.author	Elder, EE	en_US
dc.contributor.author	Boyle, FM	en_US
dc.contributor.author	Marsh, DJ https://orcid.org/0000-0001-5899-4931	en_US
dc.contributor.author	Baxter, RC	en_US
dc.date.issued	2013-02-01	en_US
dc.identifier.citation	British Journal of Cancer, 2013, 108 (2), pp. 351 - 360	en_US
dc.identifier.issn	0007-0920	en_US
dc.identifier.uri	http://hdl.handle.net/10453/127598
dc.description.abstract	Background:Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features.Methods:To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed.Results:From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer.Conclusion:This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients. © 2013 Cancer Research UK. All rights reserved.	en_US
dc.relation.ispartof	British Journal of Cancer	en_US
dc.relation.isbasedon	10.1038/bjc.2012.552	en_US
dc.subject.classification	Oncology & Carcinogenesis	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Breast Neoplasms	en_US
dc.subject.mesh	Lymphatic Metastasis	en_US
dc.subject.mesh	Calcium-Binding Proteins	en_US
dc.subject.mesh	Neoplasm Proteins	en_US
dc.subject.mesh	Ubiquitin	en_US
dc.subject.mesh	Tumor Markers, Biological	en_US
dc.subject.mesh	Prognosis	en_US
dc.subject.mesh	Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization	en_US
dc.subject.mesh	Proteomics	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Aged, 80 and over	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Biomarkers, Tumor	en_US
dc.title	Tissue biomarkers of breast cancer and their association with conventional pathologic features	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	108	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
utslib.for	1117 Public Health and Health Services	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	108	en_US

Abstract:

Background:Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features.Methods:To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed.Results:From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer.Conclusion:This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients. © 2013 Cancer Research UK. All rights reserved.

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http://hdl.handle.net/10453/127598